Trainor C, Silverman M
Am J Physiol. 1982 May;242(5):F436-46. doi: 10.1152/ajprenal.1982.242.5.F436.
The permselectivity of the postglomerular capillary wall was studied by performing pulse-injection multiple indicator-dilution experiments on dog kidneys in vivo, using simultaneous injection of T1824-labeled albumin (plasma reference), creatinine (extracellular reference), and one or two radioactively labeled indicators: raffinose (595 dalton), vitamin B12 (1,357 dalton), or inulin (approximately 5,000 dalton). The urine transit patterns superimposed for all these except albumin, suggesting equal permeability for these molecular weight markers at the level of the glomerular filtration barrier. But the renal vein mean transit times progressively decreased. Therefore, their apparent interstitial volumes of distribution decrease with increasing molecular weight. This could be due to several factors acting singly or in combination: reduced capillary permeability in the postglomerular microcirculation; restricted diffusion in the postglomerular interstitium; or excluded volume effects. Evidence suggested that the effect was due to a combination of permeability and exclusion volume effects. To assess the validity of this assumption, the barrier-limited model was compared with the experimental data. The results were analyzed (both hydropenic and mannitol-diuretic dogs) and best fits calculated using two independent parameters, permeability and excluded volume. For permeability (X10(-4) cm/s, mean +/- SD) the range of values was always greater than or equal to 15 for creatinine and raffinose, and greater than or equal to 12 for B12. The permeability for inulin was 6.9 +/- 1.4. When interstitial volume excluded was expressed as percentage of the volume available to creatine, the excluded volume was negligible for raffinose and B12 but 12 +/- 5% for inulin. During mannitol diuresis the permeability for creatinine and raffinose remained high, but the values tended to decrease for B12. The permeability of inulin decreased to 2.9 +/- 0.09. Mannitol diuresis increased the excluded volume of inulin but did not alter the creatinine, raffinose, or B12 value.
通过对犬肾进行体内脉冲注射多指示剂稀释实验，同时注射T1824标记的白蛋白（血浆参考物）、肌酐（细胞外参考物）以及一种或两种放射性标记指示剂：棉子糖（595道尔顿）、维生素B12（1357道尔顿）或菊粉（约5000道尔顿），研究了肾小球后毛细血管壁的通透选择性。除白蛋白外，所有这些物质的尿液转运模式叠加在一起，表明在肾小球滤过屏障水平，这些分子量标志物的通透性相同。但肾静脉平均转运时间逐渐缩短。因此，它们的表观间质分布容积随分子量增加而减小。这可能是由几种单独或共同作用的因素导致的：肾小球后微循环中毛细血管通透性降低；肾小球后间质中扩散受限；或排阻体积效应。有证据表明，这种效应是通透性和排阻体积效应共同作用的结果。为评估这一假设的有效性，将屏障限制模型与实验数据进行了比较。对结果进行了分析（禁水犬和甘露醇利尿犬），并使用通透性和排阻体积这两个独立参数计算出最佳拟合值。对于通透性（×10⁻⁴cm/s，平均值±标准差），肌酐和棉子糖的值范围始终大于或等于15，维生素B12的值范围大于或等于12。菊粉的通透性为6.9±1.4。当以肌酸可利用体积的百分比表示排阻的间质体积时，棉子糖和维生素B12的排阻体积可忽略不计，但菊粉为12±5%。在甘露醇利尿期间，肌酐和棉子糖的通透性仍然很高，但维生素B12的值趋于降低。菊粉的通透性降至2.9±0.09。甘露醇利尿增加了菊粉的排阻体积，但未改变肌酐、棉子糖或维生素B12的值。
